Sterile surgical technique for shunt placement reduces the shunt infection rate in children: preliminary analysis of a prospective protocol in 115 consecutive procedures

Objective The objective of this study was to evaluate whether the rigid application of a sterile protocol for shunt placement was applicable on a routine basis and allowed the reduction of shunt infections (SI) in children. Materials and methods Since 2001, a rigid sterile protocol for shunt placement in children using neither antibiotic-impregnated catheters nor laminar airflow was prospectively applied at Erasme Hospital, Brussels, Belgium. For assessing the protocol efficacy before continuation, we preliminarily analyzed the results of the first 100 operated children (43 females, 57 males, 49 aged <12 months; 115 consecutive shunt placement/revision procedures). All procedures were performed by the same senior surgeon, one assistant, one circulating nurse, one anesthesiologist. The sterile protocol was rigidly imposed to these four staff members: uniformed surgical technique; limited implant and skin edge manipulation; minimized human circulation in the room; scheduling surgery as first morning operation; avoiding postoperative cerebrospinal fluid (CSF) leak; double gloving; procedures of less than 30-min duration; systemic antibiotics prophylaxis. We analyzed separately: (1) children carrying an increased risk of SI (n = 38) due to preoperative external ventricular drainage, CSF leak, meningitis, glucocorticoids, chemotherapy; (2) children aged <12 months; (3) procedures for shunt revision. Results Errors in protocol application were recorded in 71/115 procedures. They were mainly done by non-surgical staff, decreased with time and were medically justified in some young children. Surprisingly, no SI occurred (follow-up, 4 to 70 months). One child developed an appendicitis with peritonitis (Streptococcus faecalis) after 6 months. No SI was found. After peritonitis was cured, shunt reinsertion was uneventful. Conclusion These preliminary results suggest that a uniform and drastic sterile surgical technique for shunt placement: (1) can be rigidly applied on a routine basis; (2) can lower the early SI rate below 1%; (3) might have a stronger impact to reduce SI than using antibiotic-impregnated catheters and optimizing the operative environment such as using laminar airflow and reducing the non-surgical staff. This last issue will be evaluated further in the present ongoing protocol.     

Differential modification of muscarinic cholinergic receptors in the hippocampus of patients with Alzheimer''s disease: an autoradiographic study

We have used quantitative light microscopic autoradiographic techniques to analyze changes in muscarinic cholinergic receptors in the hippocampus in Alzheimer type dementia (ATD). The density and distribution of muscarinic cholinergic receptors has been correlated with the density of neurons, neuritic plaques and neurofibrillary tangles in the CA1 subfield of the hippocampus of control and ATD patients. The number of pyramidal cells per mm² in the CA1 sector was significantly decreased in ATD cases as compared to controls, although there were large variations among cases. The most marked reductions in cell counts were observed in patients with a history of profound dementia. The densities of muscarinic receptors, as well as the proportions of M₁ and M₂ subtypes, in the CA1 sector and dentate gyrus were not significantly different between ATD and old non-demented patients. Neuritic plaques, even in high numbers, did not affect the density of muscarinic receptors; moreover, the densities of receptors over the neuritic plaques did not differ from the surrounding neuropil. However, in some ATD cases there was a marked decrease in the concentration of these receptors in the CA1 sector and subiculum, with no change in the proportions of muscarinic receptor subtypes. These patients exhibited frequent extracellular remnants of neurofibrillary tangles (ghost tangles), but scarce neuritic plaques, and were those showing severe losses of pyramidal cells. There was a significant positive correlation between the total concentration of muscarinic receptors in the CA1 and the density of pyramidal cells, suggesting that decreases in receptor concentration result from a severe neuronal loss. We observed that the ratio of muscarinic receptors per pyramidal cell was significantly increased in ATD patients. This might indicate a possible upregulatory mechanism for muscarinic receptors in the population of remaining neurons in ATD. However, decreases of receptor numbers following severe neuronal fall out suggest that compensatory mechanisms are no longer possible in such cases. The question is raised whether these differences between cases reflect different diseases or different stages of the same disease.     

Randomized double-blind study comparing the effectiveness of balloon dilation of the prostate and cystoscopy for the treatment of symptomatic benign prostatic hyperplasia.

We attempted to determine the effectiveness of balloon dilation of the prostate for the treatment of symptomatic benign prostatic hyperplasia (BPH). A total of 33 men with symptomatic BPH signed informed consent to participate in a randomized, double-blind study comparing balloon dilation of the prostate and cystoscopy. Balloon dilation of the prostate and cystoscopy were performed with the patient under intravenous sedation after intraurethral instillation of viscous lidocaine and infiltration of the autonomic neural innervation of the prostate with 1% lidocaine. Efficacy was based upon improvement in Boyarsky symptom scores, increases in peak urinary flow rates and patient global assessment of symptomatic improvement. Efficacy was assessed at 1 and 3 months after treatment. A study nurse blinded to the randomization scheme administered the symptom score questionnaires and supervised the uroflowmetry studies. The study was randomized, since the mean baseline prostate sizes, peak urine flow rates, obstructive and irritative symptoms scores, post-void residual volumes and patient ages were similar in the 2 groups. The patient perceptions of treatment rendered were similar for the 2 treatment groups, confirming that the study was double-blind. The patients undergoing cystoscopy and balloon dilation of the prostate experienced a statistically significant improvement in the mean total symptom scores at 1 and 3 months. The mean total symptom scores after balloon dilation of the prostate and cystoscopy at 1 and 3 months were not significantly different. The mean peak urinary flow rates 1 and 3 months after balloon dilation of the prostate and cystoscopy were not significantly different from the baseline mean peak urinary flow rates. We demonstrate that balloon dilation of the prostate and cystoscopy are equally effective for the treatment of BPH. Since cystoscopy is considered a diagnostic modality, our study suggests that the efficacy previously observed after balloon dilation of the prostate is primarily placebo-related. The study does not support the indication of balloon dilation of the prostate for the treatment of symptomatic BPH.     

Characterization of rat hyperplastic bile ductular epithelial cells in culture andin vivo

A novel intrahepatic biliary cell culture/in vivo transplantation system has been developed with an essentially pure population of bile ductular epithelial cells isolated from rat liver 6–12 weeks after bile duct ligation. In primary culture, these cells retain staining strongly for -glutamyltranspeptidase and glutathione S-transferase P. The cytoplasm of cultured bile ductular cells reacts with an anti-laminin antibody, but loses immunoreactivity with a monoclonal anti-cytokeratin 19 antibody. Semiconservative DNA synthesis in the cultured cells was dependent upon the continued presence of 10% fetal calf serum in the medium. Replicating bile ductular cells could be subcultured for a finite number of passages. In addition, freshly isolated bile ductular epithelial cells gave rise to well differentiated bile ductular structures when transplanted into the interscapular fat pads of syngeneic recipient rats.Presented at the Proceedings of the International Meeting on Normal and Neoplastic Growth in Hepatology, Bari, Italy, June 1989.This work was supported by USPHS Grant RO1 CA39225 to Dr. Sirica by the National Cancer Institute, Department of Health and Human Services.     

Paclitaxel decreases the interstitial fluid pressure and improves oxygenation in breast cancers in patients treated with neoadjuvant chemotherapy: clinical implications.

PURPOSE: It has been hypothesized that tumors with high interstitial fluid pressure (IFP) and/or hypoxia respond poorly to chemotherapy (CT) because of poor drug delivery. Preclinical studies have shown that paclitaxel reduces the IFP and improves the oxygenation (pO(2)) of tumors. Our aim is to evaluate the IFP and pO(2) before and after neoadjuvant CT using sequential paclitaxel and doxorubicin in patients with breast cancer tumors of >/= 3 cm. PATIENTS AND METHODS: Patients were randomly assigned, according to an institutional review board-approved phase II protocol, to receive neoadjuvant sequential CT consisting of either four cycles of dose-dense doxorubicin at 60 mg/m(2) every 2 weeks followed by nine cycles of weekly paclitaxel at 80 mg/m(2) (group 1) or vice versa, with paclitaxel administered before doxorubicin (group 2). Patients were re-evaluated clinically and radiologically. The IFP (wick-in-needle technique) and pO(2) (Eppendorf) were measured in tumors at baseline and after completing the administration of the first and second drug. RESULTS: IFP and pO(2) were measured in 54 patients at baseline and after the first CT. Twenty-nine and 25 patients were randomly assigned to groups 1 and 2, respectively. Paclitaxel, when administered first, decreased the mean IFP by 36% (P = .02) and improved the tumor pO(2) by almost 100% (P = .003). In contrast, doxorubicin did not have a significant effect on either parameter. This difference was independent of the tumor size or response measured by ultrasound. CONCLUSION: Paclitaxel significantly decreased the IFP and increased the pO(2), whereas doxorubicin did not cause any significant changes. Tumor physiology could potentially be used to optimize the sequence of neoadjuvant CT in breast cancer.     

Molecular modeling of 5-HT3 receptor ligands.

Ligands of various chemical classes (e.g., indoles, indazoles, benzamides, carbazoles, and quinolines) have demonstrated high affinity for the 5-HT₃ receptor in radiolabeled ligand-binding studies, and have shown 5-HT₃ receptor antagonistic activity in functional assays which utilize the excitatory effects of 5-HT on enteric neurons and autonomic afferents. Several 5-HT₃ antagonists are currently being evaluated for potential use in the treatment of migraine, schizophrenia, and anxiety, and a few have already demonstrated high efficacy as antiemetics in cancer chemotherapy. The purpose of this presentation is to highlight the significant structure-affinity relationships (SAFIR) and common geometrical features among 5-HT₃ receptor ligands, and to describe the three-dimensional pharmacophore for the 5-HT₃ recognition site derived from computational techniques. The chemical template containing the recognition elements (functional groups) for the 5-HT₃ receptor are: an aromatic or heteroaromatic ring system, a coplanar carbonyl group, and a nitrogen center, interrelated by well-defined distances. Two “binding shapes” or “active shapes” for 5-HT₃ ligands have been identified from detailed conformational analyses.